Preterm birth is a major public-health issue because of its increasing incidence combined with the frequent occurrence of subsequent behavioral, neurological, and psychiatric challenges faced by surviving infants. Approximately 10-15% of very preterm children (born <30 weeks gestational age) develop cerebral palsy, and 30 - 60% of very preterm children experience cognitive impairments. These impairments include visual-motor problems, attentional difficulties, impaired memory, delayed acquisition of language, executive dysfunction, learning disabilities, poor social skills, and higher rates of social withdrawal, anxiety and depression. In addition, an increased prevalence of developmental disorders such as attention deficit/hyperactivity disorder, autism and schizophrenia, has been described in the preterm population. A greater understanding of the mechanisms leading to neurobehavioral impairments in preterm children is an important step in developing strategies for improving clinical outcomes. We have a unique, large cohort of 229 preterm infants (<30 weeks gestation or <1250g) for whom we have developed an extensive perinatal database and obtained advanced magnetic resonance (MR) images at term equivalent. Evaluation of these data has led to novel insights into the nature of the cerebral lesion associated with preterm birth. Importantly, we have maintained ongoing contact with 97% of this cohort during the course of longitudinal neuropsychological follow up. This population now offers a rare opportunity for longitudinal evaluation of the mechanisms of neurobehavioral impairment in association with modern, advanced MR imaging methods. We propose to apply state-of-the-art MR imaging methods to this cohort at 6 years of age in conjunction with neuropsychological evaluation. The MR data will allow us to study the evolution of structural changes in the brain from term equivalent into childhood in both the preterm and term born infants. The techniques will include surface based morphometry (SBM), brain volume measurements (volumetry), and diffusion tensor imaging (DTI). The MR approaches will provide both macroscopic (volumes and SBM) and microscopic (DTI) measures of cerebral development that address different aspects of brain structure and maturation. These will be related to the longitudinal social and neuropsychological evaluations to investigate the relationship of MR measures to neurobehavioral impairments. The longitudinal design will allow us to study both structural abnormalities and compensatory changes over childhood in response to early brain injury. These data will likely provide new understanding of neural recovery and strategies for improving outcomes in preterm infants. PUBLIC HEALTH RELEVANCE: This study is designed to use magnetic resonance (MR) imaging to improve our understanding of the brain injury sustained by prematurely-born infants and how the brain subsequently develops over childhood. The longitudinal design, using both advanced MR imaging and psychological testing, will allow us to study both structural abnormalities and positive adaptive changes over childhood in response to early brain injury. This will assist us in understanding how to reduce the global and specific disabilities that these vulnerable children later face.